The term “Induced pluripotent stem cells,” or iPSCs, refers to a type of pluripotent stem cell artificially prepared from a non-pluripotent cell. Cardiac myocytes derived from iPSCs are a useful experimental system which has great potential. They offer an innovative human preparation for cardiac repair, drug safety design and testing, clinical diagnosis, and research. Cardiac myocytes derived from iPSCs offer the opportunity to work on cells which recapitulate the activity of healthy human cardiac myocytes, which are otherwise rarely available for comprehensive experimental investigation. Human iPSC-derived cardiac myocytes offer the ability to develop predictive tools for cardiac function.
Despite the possibilities of cardiac myocytes derived from iPSCs, problems with this approach have been noted, leading to serious concerns about their use in studying arrhythmogenic mechanisms and drug safety screening. Action potentials (APs) from human cardiac myocytes derived from iPSCs are often referred to as an “immature phenotype.” The lack of the expected classic spike and dome type of AP morphology has led to serious concerns over the ability of human cardiac myocytes derived from iPSCs to be used to study the genetic basis of Brugada syndrome and other J-wave or early repolarization related arrhythmias. In addition to an apparently less complicated repolarization profile, iPSC cardiac myocytes also show spontaneous contractile activity. This contractile activity is accompanied by corresponding diastolic depolarization resulting in spontaneous APs. Thus, while iPSCs can be induced to develop into cardiac myocyte-like cells, they are not able to display electrophysiological properties that would allow use of these cells in evaluation of cardiac cell function or use for screening of drugs affecting cardiac cells.